This invention relates to the immune system and, more specifically, to methods of modifying pathological immune responses in psoriasis.
Higher organisms are characterized by an immune system which protects them against invasion by potentially-deleterious substances or microorganisms. When a substance, termed an antigen, enters the body, and is recognized as foreign, the immune system mounts both an antibody-mediated response and a cell-mediated response. Cells of the immune system termed B lymphocytes, or B cells, produce antibodies that specifically recognize and bind to the foreign substance. Other lymphocytes termed T lymphocytes, or T cells, both effect and regulate the cell-mediated response resulting eventually in the elimination of the antigen.
A variety of T cells are involved in the cell-mediated response. Some induce particular B cell clones to proliferate and produce antibodies specific for the antigen. Others recognize and destroy cells presenting foreign antigens on their surfaces. Certain T cells regulate the response by either stimulating or suppressing other cells.
While the normal immune system is closely regulated, aberrations in immune response are not uncommon. In some instances, the immune system functions inappropriately and reacts to a component of the host as if it were, in fact, foreign. Such a response results in an autoimmune disease, in which the host""s immune system attacks the host""s own tissue. T cells, as the primary regulators of the immune system, directly or indirectly effect such autoimmune pathologies.
Psoriasis is characterized by epidermal keratinocyte hyperproliferation, coupled with an inflammatory infiltrate. The pathogenesis of this disease is not fully understood. T cell activation appears to play a vital role in triggering and/or maintaining the disease. As evidence, cyclosporin A works effectively on improving the patient""s condition.
A need exists for improved and effective means of curing or ameliorating psoriasis. Such a treatment should ideally control the inappropriate T cell response, rather than merely reducing the symptoms. The present invention satisfies this need and provides related advantages as well.
This invention provides methods of preventing or reducing the severity of psoriasis in an individual by administering a peptide having substantially the sequence of a T cell receptor present on the surface of T cells mediating psoriasis which is capable of causing an effect on the immune system to regulate the T cells.
This invention provides methods of preventing or reducing the severity of psoriasis in an individual by administering a peptide having substantially the sequence of a non-conserved region sequence of a T cell receptor present on the surface of T cells mediating psoriasis or a fragment thereof, wherein the peptide or fragment is capable of causing an effect on the immune system to regulate the T cells.
This invention also provides compositions for preventing or reducing the severity of psoriasis in an individual having a peptide having substantially the sequence of a non-conserved region of a T cell receptor present on the surface of T cells mediating psoriasis or a fragment thereof, wherein the peptide or fragment is capable of causing an effect on the immune system to regulate the T cells.
In another embodiment, this invention concerns methods of preventing the proliferation of T cells associated with psoriasis in an individual by determining a T cell receptor binding partner for a T cell receptor present on the surface of T cells mediating psoriasis and administering the T cell binding partner to the individual.
According to another embodiment, the method involves preventing or reducing the severity of psoriasis by inhibiting the binding of a T cell receptor to its TCR binding partner in order to prevent the proliferation of T cells associated with psoriasis.
This invention also provides methods of preventing or reducing the severity of psoriasis in an individual by contacting T cells specifically associated with psoriasis with an effective amount of a cytotoxic or cytostatic agent specifically reactive with such T cells to inhibit their activity.
This invention further provides methods of diagnosing or predicting susceptibility to psoriasis in an individual by detecting T cells having a T cell receptor associated with psoriasis in a sample from the individual, the presence of abnormal expression of T cells containing the T cell receptor indicating the pathology or susceptibility to psoriasis.
This invention provides methods of preventing or reducing the severity of psoriasis in an individual by preventing the attachment of a psoriasis-associated T-cell receptor to its binding partner.
Another method of this invention involves preventing or reducing the severity of psoriasis in an individual by administering to the individual a vector having an expression control sequence operatively linked to a nucleic acid encoding a T cell receptor or a peptide having substantially the sequence of a non-conserved region sequence of a T cell receptor present on the surface of T cells mediating psoriasis or a fragment thereof, wherein the peptide or fragment is capable of causing an effect on the immune system to regulate the T cells.
This invention also provides vectors having an expression control sequence operatively linked to a nucleic acid encoding a T cell receptor or a peptide having substantially the sequence of a non-conserved region sequence of a T cell receptor present on the surface of T cells mediating psoriasis.